This invention relates to a method for producing and isolating 5,6-diacetoxyindole (DAI) in a single reaction vessel using 3,4-dihydroxyphenylalanine (dopa) as a starting material.
DAI is well known as a stable melanin precursor that is useful as a hair dye. However, prior known methods of producing and isolating DAI have disadvantages that have discouraged its use on an industrial scale. Such methods typically involve multiple steps that must be performed in several reaction vessels. As a result, those methods for producing DAI are costly and time-consuming.
For example, Beer, R. J. S. et. al., J. Chem. Soc., 2223-26 (1948) discloses the production of DAI by reductive cyclization of 4,5-diacetoxy-2,.beta.-dinitrostyrene (a material that itself must first be synthesized) with iron in acetic acid and absolute alcohol. The reaction mixture was filtered and the filtrate was diluted with water, basified with sodium hydrogen carbonate, and extracted five times with ether. The mixture was evaporated to give a viscous gum that partially crystallized when placed in a vacuum. The DAI crystals were purified by being extracted several times with hot light petroleum-containing benzene.
Similarly, Murphy, Bryan P., J. Org. Chem., 50, 5873-75 (1985), discloses a multistep procedure which, using piperonal as a starting material, yields DAI only after acetylation of the resulting mixture, removal of the solvent in vacuo, and HPLC purification. See also, for example, Burton, H. et. al., J. Chem. Soc., 78-9 (1949); Burton, H. et. al., J. Chem. Soc., 1062-64 (1950); Ek, Arvid et. al., J. Amer. Chem. Soc., 76, 5579-88 (1954); Shaw, Kenneth N. F. et. al., Biochem. Prep., 9, 12-21 (1962); and Suvorov, N. N et. al., Zh. Obshch. Khim., 30, 3118-23 (1960).